Tuttle KR, et al. - In patients with type 2 diabetes and moderate-to-severe chronic kidney disease, researchers tested the effectiveness and safety of dulaglutide. Findings revealed that once-weekly dulaglutide produced glycemic control similar to that achieved with insulin glargine, with a decreased decline in estimated glomerular filtration rate (eGFR) in these patients. In patients with moderate-to-severe chronic kidney disease, dulaglutide appeared to be safe to use to achieve glycemic control.

Methods

• AWARD-7 was a multicenter, open-label trial performed at 99 sites in nine countries.
• Included patients were adults with type 2 diabetes and moderate-to-severe chronic kidney disease (stages 3–4), with an HbA_1c of 7.5–10.5%, who were being treated with insulin or insulin plus an oral antihyperglycemic drug, and were taking a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.
• Participants in the study were randomly assigned (1:1:1) via a computer-generated random sequence with an interactive response system to once-weekly injectable dulaglutide 1.5 mg, once-weekly dulaglutide 0.75 mg, or daily insulin glargine as basal therapy, all in combination with insulin lispro, for 52 weeks.
• Insulin glargine and lispro doses were titrated as per an adjustment algorithm.
• Dulaglutide doses were masked to participants and investigators.
• HbA_1c at 26 weeks, with a 0.4% non-inferiority margin was the primary outcome.
• eGFR and urine albumin-to-creatinine ratio (UACR) were the included secondary outcomes.
• The primary analysis population was all randomly assigned subjects who received at least one dose of study treatment and had at least one post-randomization HbA_1cmeasurement.
• The safety population was all subjects who received at least one dose of study treatment and had any post-dose data.

Results

• Five hundred seventy-seven patients were randomly assigned, 193 to dulaglutide 1.5 mg, 190 to dulaglutide 0.75 mg, and 194 to insulin glargine between August 15, 2012 and November 30, 2015.
• At 26 weeks, the impact on HbA_1c change with dulaglutide 1.5 mg and 0.75 mg were non-inferior to those of insulin glargine (least squares mean [LSM] -1.2% [SE 0.1] with dulaglutide 1.5 mg [183 patients]; -1.1% [0.1] with dulaglutide 0.75 mg [180 patients]; -1.1% [0.1] with insulin glargine [186 patients]; one-sided p≤ 0.0001 for both dulaglutide doses vs insulin glargine).
• Findings revealed that the differences in HbA_1cconcentration at 26 weeks between dulaglutide and insulin glargine treatments were LSM difference -0.05% (95% CI -0.26 to 0.15, p < 0.0001) with dulaglutide 1.5 mg and 0.02% (-0.18 to -0.22, p=0.0001) with dulaglutide 0.75 mg.
• Data reported that HbA_1c-lowering impacts persisted to 52 weeks (LSM -1.1% [SE 0.1] with dulaglutide 1.5 mg; -1.1% [0.1] with dulaglutide 0.75 mg; -1.0% [0.1] with insulin glargine).
• At 52 weeks, eGFR was higher with dulaglutide 1.5 mg (Chronic Kidney Disease Epidemiology Collaboration equation by cystatin C geometric LSM 34.0 mL/min per 1.73 m² [SE 0.7]; p=0.005 vs insulin glargine) and dulaglutide 0.75 mg (33.8 mL/min per 1.73 m² [0.7]; p=0.009 vs insulin glargine) than with insulin glargine (31.3 mL/min per 1.73 m² [0.7]).
• At 52 weeks, the impacts of dulaglutide 1.5 mg and 0.75 mg on UACR reduction were not significantly different from that of insulin glargine (LSM -22.5% [95% CI -35.1 to -7.5] with dulaglutide 1.5 mg; -20.1% [-33.1 to -4.6] with dulaglutide 0.75 mg; -13.0% [-27.1 to 3.9] with insulin glargine).
• Researchers found that proportions of patients with any serious adverse events were similar across groups (20% [38 of 192] with dulaglutide 1.5 mg, 24% [45 of 190] with dulaglutide 0.75 mg, and 27% [52 of 194] with insulin glargine).
• They discovered that dulaglutide was related to higher rates of nausea (20% [38 of 192] with dulaglutide 1.5 mg and 14% [27 of 190] with 0.75 mg, vs 5% [nine of 194] with insulin glargine) and diarrhea (17% [33 of 192] with dulaglutide 1.5 mg and 16% [30 of 190] with 0.75 mg, vs 7% [14 of 194] with insulin glargine) and lower rates of symptomatic hypoglycemia (4.4 events per patient per year with dulaglutide 1.5 mg and 4.3 with dulaglutide 0.75 mg, vs 9.6 with insulin glargine).
• As per data, end-stage renal disease occurred in 38 participants: eight (4%) of 192 with dulaglutide 1.5 mg, 14 (7%) of 190 with dulaglutide 0.75 mg, and 16 (8%) of 194 with insulin glargine.